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Re:Delaying a Covid vaccine’s second dose boosts immune resp... by wutbrodo on Friday May 14, 2021 @02:17PM (#27157778)
Some more info from the uni that performed the study[1]:

> In relation to the cellular (or T cell) immune response, which plays an important role in supporting and maintaining antibody production, the team found that within the three-week interval group, 60% had a confirmed cellular response at two to three weeks following the second vaccine - although this fell to only 15% eight to nine weeks later.

> The proportion of participants showing a cellular response in the 12-week-interval group was only eight per cent at five to six weeks after the first vaccine, but this rose to 31% two to three weeks after the second vaccine. Research is required to further explore these variations in responses.

You're correct that the evidence isn't dispositive yet, but it's an encouraging signal. Antibody response in the short-term is positive and in the medium-term cellular response possibly converges.

More importantly, the implications for the first doses first strategy are positive. Those who know how to reason under uncertainty saw the UK's strategy as a calculated gamble based on a model that extended the point information provided by the vaccine efficacy RCT; critics were generally incoherent but their claim was that it was likely to cause large _negative_ effects on efficacy, worth paying the cost of vaccinating far fewer people.

On top of the priors that led to the decision, we now have signal from the way the winter surge played out in the UK, and the increased antibody response alone provides further weak signal that the delay was worth it - and conversely, that the US's approach cost lives).

The evidence still isn't dispositive, but crucially, there's no such strong basis for believing the alternative either: that extending doses _reduces_ efficacy and that vaccine availability should be limited in the name of adhering rigidly to the RCT-studied timeline.

The status quo bias of medical culture killed a lot of people during this pandemic by continuing their habit of pretending that certainty exists where none does and refusing to engage in critical thinking about uncertainty. Refusing to explicitly extrapolate a model from few high-quality samples really just means "implicitly extrapolating a crappy model through bias and guesswork". This may be adaptive in the normal medical context, where the status quo is generally fine, but is an incredibly poor fit for a fast-moving pandemic that was killing thousands a day in the US alone.

[1] https://www.birmingham.ac.uk/news/latest/2021/05/covid-pfize...

Re:Delaying a Covid vaccine’s second dose boosts immune resp... by arcticfox on Friday May 14, 2021 @02:51PM (#27158261)
I completely agree with everything you said.

That said, the most effective defense I've seen for the seemingly incoherently cautious status quo approach is that the medical community doesn't operate on the span of one pandemic, but is rather in a perpetual struggle. So even if the short-term expected value of an excessively cautious approach is negative, resulting in more deaths and a longer pandemic, it might be outweighed by reducing the chance of damaging public faith in medicine long-term by an erroneous more aggressive move.

I still don't agree, but that very long-term view is the only defense I see for the approach given what we knew at the time.

Re:Delaying a Covid vaccine’s second dose boosts immune resp... by wutbrodo on Friday May 14, 2021 @04:47PM (#27159509)
Thank you for bringing that up. That makes a lot of sense, and public health absolutely does need to consider mass psychology and their credibility.

The theory that they're overindexing on protecting that credibility doesn't really comport with their behavior the rest of pandemic, however. Leaving aside all of the blood on the hands of mindless bureaucracy (like effectively banning testing for Covid in the early pandemic when it was most crucial), there has been decision after decision that prioritized status quo bias and RCT-worship even when the long game suggests it would damage their credibility (the fervent anti-mask recommendations in the early pandemic is a great example, as is the bizarre insistence on recommending precautions against fomites over aerosols until extremely late).

More importantly, "public health is misleading you at the cost of your health/life because they're playing the long game" doesn't actually preserve much credibility. It certainly casts public health figures in a more positive light, but I'm not really thinking in terms of blaming individuals over institutions/cultures anyway. It doesn't really matter _why_ public health advice is wrong in obvious and significant ways. What matters is the ultimate conclusion: if you have basic scientific literacy and an IQ over 105, form your own broad understanding of the science. This isn't a call to jettison epistemic humility: you're not going to be able to understand things anywhere close to as well as an individual epidemiologist can. But the point is that listening to the science as filtered through public health advice _is even worse_, in the same way that getting nutrition advice from the USDA will.

Re:Delaying a Covid vaccine’s second dose boosts immune resp... by Scoundreller on Friday May 14, 2021 @11:52PM (#27162188)
> as is the bizarre insistence on recommending precautions against fomites over aerosols until extremely late

I watched Contagion for the first time last week, and they had the same attitude toward fomites, where it was spread through knobs and cash registers.

I’m convinced that the movie was interpreted as a documentary on what to do rather than science.

Now I question how much hand-washing helps prevent the spread of other respiratory viruses.

Looks like, for flu, in this study, fomites were responsible for 4% of cases:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6121424/

… and

> Mask wearing is much more useful than hand washing for control of influenza A in the tested office setting. Regular cleaning of high-touch surfaces, which can reduce the infection risk by 2.14%, is recommended and is much more efficient than hand-washing.

But I’m just a guy that spent 2 minutes searching studies on Google of respiratory viruses, why make decisions so easily based on that when you can base decisions on a movie on Netflix.

Re:Delaying a Covid vaccine’s second dose boosts immune resp... by wutbrodo on Saturday May 15, 2021 @05:21AM (#27163674)
Very interesting, thank you. Call it Gell-Mann Amnesia, but I had not thought to extend my skepticism of the basic competence of public health authorities to flu recommendations. I suppose my model is that they were bad in the fast-moving epistemic environment of the pandemic, and that this wouldn't extend to relatively stable and well-understood cases like influenza.
Re:Delaying a Covid vaccine’s second dose boosts immune resp... by UncleOxidant on Friday May 14, 2021 @05:20PM (#27159842)
Isn't there a potential downside to the UK approach in an environment where variants are increasing? I've seen some data suggesting that with only one jab the mRNA vaccines are only about 20% effective against the UK, SA and Brazilian variants (no data yet on the India variant), but that number jumps in to the 70% range with the 2nd dose. A delay of 12 weeks leaves a lot of people in that 20% efficacy range for those variants. Now some parts of the UK are starting to see increasing cases of the Indian variant.
Re:Delaying a Covid vaccine’s second dose boosts immune resp... by eightysixfour on Friday May 14, 2021 @07:11PM (#27160633)
Do you have a source for this number? All of the evidence I've seen shows the mRNA vaccines are in the 80% effectiveness range after a single dose, but that data was not specific to any variants.
Re:Delaying a Covid vaccine’s second dose boosts immune resp... by UncleOxidant on Friday May 14, 2021 @07:53PM (#27160907)
One study from Qatar: https://www.nejm.org/doi/full/10.1056/NEJMc2104974

    For preventing infection:
    B.1.1.7: 29.5% effective after one dose (Pfizer) 
    B.1.351: 16.9%
See Table 1 there for more details.
Re:Delaying a Covid vaccine’s second dose boosts immune resp... by eightysixfour on Friday May 14, 2021 @08:58PM (#27161277)
Would have been really nice if they had separated the effectiveness data by days after first dose, we know the curve is substantial for the first few weeks so it would not be surprising for people to still catch it in week one, I would be surprised by data showing <50% effectiveness in week three and four.
Re:Delaying a Covid vaccine’s second dose boosts immune resp... by eightysixfour on Saturday May 15, 2021 @07:13PM (#27169798)
Re:Delaying a Covid vaccine’s second dose boosts immune resp... by graeme on Saturday May 15, 2021 @08:48AM (#27164721)
I believe the author said people were misinterpreting the study. It included people who caught it before the protection of the first dose kicked in.
Re:Delaying a Covid vaccine’s second dose boosts immune resp... by wutbrodo on Friday May 14, 2021 @06:38PM (#27160416)
> with only one jab the mRNA vaccines are only about 20% effective against the UK, SA and Brazilian variants

Do you have a source for this I could see? I did some light Googling and couldn't find anything that said as much; it also runs contrary to the impact of Britain's choice of widespread vaccination over incremental effectiveness gains (though this is of course just a correlation). A study I did find[1] looking at effectiveness in the UK has first-dose effectiveness at 70%, roughly as expected (I'm using the UK here as a noisy proxy for the UK variant, but I think that's reasonable).

Leaving aside the veracity of this concern, the counterfactual was facing the massive winter surge many countries saw while intentionally choosing to vaccinate half as many people. It's not clear at all that it would be good policy, especially given the ability to change policy[2] as the reality on the ground changes. Seeing how public health has conducted themselves throughout pandemic, I simply don't have the blind faith that they handled this cost-benefit analysis competently.

To pick just one example I came across[3]: as much as I respect Bob Wachter, the Chair of Medicine at UCSF, he was exemplary of this flaw in critical thinking ability that medical culture indoctrinates into HCWs. He came around to FDF on New Year's, after a month of arguing against it. It's amazing to see him discover the concept of quantitative rigor in the face of uncertainty when speed is crucial. This is especially striking when contrasted against his prior argument in the opposite direction, which consists of handwavy platitudes around "unnecessary curveballs".

My sister and her husband are both (Ivy League-educated, very successful) physicians, one a clinician and one a clinician scientist. We've had a decade-long conversation about this tendency, the degree to which it exists, the degree to which it's salutary, how it should affect patient/informed-citizen behavior, etc. Part of my relative confidence in my model of this epistemic culture is that these pitfalls were entirely predictable, and indeed, I pre-registered concerns[4] about the pandemic's characteristics and how modern medical culture was likely to interact with it.

This isn't as damning an indictment of medicine as it may sound (the FDA's Vogonic bureaucracy fetish has way more blood on its hands than any of the flaws in medical culture). And one thing I've picked up from all my conversations with my brother-in-law is that the average consumer of medical information is almost unbelievably stupid (not how he would phrase it) and is far better off following public health (and nutrition) advice as dogma than trying to understand and pick it apart. But if you are basically scientifically-literate, say to the point that you can read and mostly understand the paper I shared in [1], you're likely far worse off uncritically accepting their epistemic flaws than using them as a baseline and doing your own research (and as always, retain a heaping dose of epistemic humility around your error bars and counterfactuals)

[1] https://www.bmj.com/content/373/bmj.n1088

[2] https://www.nytimes.com/2021/05/14/world/india-covid-second-...

[3] https://twitter.com/Bob_Wachter/status/1344667655324585986

[4] This was in conversation with them. Sadly, I have no online proof I can share without self-doxxing

Re:Delaying a Covid vaccine’s second dose boosts immune resp... by UncleOxidant on Friday May 14, 2021 @07:53PM (#27160912)
Re:Delaying a Covid vaccine’s second dose boosts immune resp... by graeme on Friday May 14, 2021 @04:13PM (#27159183)
Is having a lower peak cellular response meaningful in the long run, or not so much?
Re:Delaying a Covid vaccine’s second dose boosts immune resp... by wutbrodo on Friday May 14, 2021 @04:52PM (#27159554)
Great question, that I don't know the answer to. The answer to that question is part of the uncertainty that attenuates the signal I described as "weak". I think the reason I like the approach I'm describing is that you can model uncertainty at every level of knowledge: you don't need to become an epidemiologist to reason about the facts (with correspondingly higher error bars than a domain expert would have), _and_ you don't need to blindly trust that experts in every domain are somehow magically optimal when it comes to reasoning under uncertainty.

To put it another way, that's the kind of information I would spend the time digging into once knowing the answer would push my model across a decision threshold. I look forward to seeing the follow-up research, which is usually the quickest way to fill in gaps in the "primitives".